Specific molecular events leading to DNA methylation during replication and their role in the biological function of DNA, possibly neoplasia, are being investigated in subnuclear fractions prepared from mouse cells in S phase. A uniquely controlled, mammalian cell culture system, in which a neoplastic line is derived from a parallel, non-neoplastic line, serves as the source of nuclear material. The ability of various subnuclear fractions to transfer a labeled methyl group from S-adenosylmethionine to a heterologous DNA acceptor is analyzed by high performance liquid chromatography.